March 2000

Advantages of Fentanyl Over Morphine in Analgesia for Ventilated Newborn Infants After Birth: A Randomized Trial

Saarenmaa E; Huttunen P; Leppaluoto J; Meretoja O; Fellman V.
J Pediatr 1999 Feb;134(2):144-50.

Commentary by Charles Coté, M.D.

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[ see abstract below ]

Saarenmaa et al compared fentanyl with morphine for analgesia given to ventilated newborns. The groups were evenly matched for age, weight, need for dopamine infusions, and a variety of other factors. The incidence of hypotension and urinary retention was similar but the incidence of gastrointestinal motility problems was significantly lower in the fentanyl group. The authors concluded that both drugs were effective in reducing the hormonal responses to stress and provided equivalent hemodynamic stability. They felt that due to the favorable kinetics and fewer side effects related to the GI system, fentanyl might offer advantages to the sick newborn requiring short-term analgesia in the NICU setting. They did not examine the true pharmacokinetics nor did they examine the pharmacodynamics for long term infusions. Of concern in that setting is the rapid development of tachyphylaxis. Withdrawal syndrome is also associated with all opioids administered for longer than 10 days. This study is an excellent example of comparing the pharmacodynamic differences without the need for a placebo control group. This certainly is the type of study that is also feasible in this very vulnerable population.

ABSTRACT Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth: A randomized trial Saarenmaa E; Huttunen P; Leppaluoto J; Meretoja O; Fellman V. SOURCE: J Pediatr 1999 Feb;134(2):144-50. COMMENT: Comment in: J Pediatr 1999 Feb;134(2):127-9. ABSTRACT: OBJECTIVE: To compare the efficacy and adverse effects of fentanyl or morphine analgesia during the first 2 days of life in newborn infants who underwent mechanical ventilation. STUDY DESIGN: In a randomized double-blind trial, 163 infants were allocated to receive a continuous infusion of fentanyl (10.5 µg/kg over a 1-hour period followed by 1.5 µg/kg/hr) or morphine (140 µg/kg over a 1-hour period followed by 20 µg/kg/hr) for at least 24 hours. The severity of pain was assessed with physiological parameters, a behavioral pain scale, and stress hormone concentrations before and 2 and 24 hours after the start of treatment. RESULTS: The analgesic effect was similar in both groups, as judged by the pain scale. Plasma adrenaline and noradrenaline concentrations decreased significantly from 0 to 24 hours in both groups. Median adrenaline decrease was 0.5 nmol/L (interquartile range [IQR] 1.1;0.0) in the fentanyl and 0.7 nmol/L (IQR 1.3;0.1) in the morphine group, noradrenaline 2.1 nmol/L (IQR 9.0;0.2), and 3.0 nmol/L (IQR 7.5;0.3), respectively. beta-endorphin decreased significantly only in the fentanyl group ( 14 pmol/L (IQR 28; 7), P <.05). Decreased gastrointestinal motility was less frequent in the fentanyl group (23% vs 47%, P <.01). CONCLUSIONS: With at least as effective analgesia as with morphine, fentanyl had fewer side effects. Fentanyl may be superior to morphine for short-term postnatal analgesia in newborn infants.